Acute effects of tumor necrosis factor on hydraulic conductivity of mammalian postcapillary venules

Background: Tumor necrosis factor (TNF) is a cytokine that has been implicated in the development of capillary leak in sepsis. Methods: We examined the direct effects of intraluminally applied TNF on microvessel hydraulic permeability (Lp) in the in situ mesentery of pentobarbital anesthetized female rats. Postcapillary venules were cannulated and perfused with Ringer's solution containing 0.5% albumin and washed erythrocytes. Transcapillary volume flow per unit surface area (Jv/S) was measured by using the modified Landis technique and Lp was calculated from the regression of Jv/S on pressures between 35 and 75 cm H₂O. Results: Under control conditions the Lp (mean ± SE) was 1.06 ± 0.08 x 10^-7 cm/(s · cm H₂O) (n = 16). Lp was 0.87 ± 0.12 x 10^-7 cm/(s · cm H₂O) after a 20-minute perfusion with murine recombinant TNF at a concentration of 150 pg/mL (n = 5, p vs. control = 0.3). At a concentration of 10 ng/mL Lp was 1.15 ± 0.15 x 10^-7 cm/(s · cm H₂O) (n = 7, p vs. control = 0.6). In vessels perfused for 2 hours with TNF at 10 ng/mL, Lp was 0.96 ± 0.33 x 10^-7 cm/(s · cm H₂O) (n = 4, p = 0.66). At 100 ng/mL, Lp was 2.4 ± 0.40 x 10^-7 cm/(s · cm H₂O) (n = 7, p = 0.046). Conclusion: The acute intraluminal exposure to TNF, in the absence of other circulating factors, does not increase venular hydraulic permeability at concentrations of 150 pg/mL and 10 ng/mL. In vessels exposed at high or supraphysiologic concentrations (100 ng/mL), an acute twofold increase in Lp was demonstrated.